Diabetic patients need to frequently monitor blood glucose levels to ensure that the levels remain within acceptable bounds and, for insulin dependent diabetics, to determine the amount of insulin that must be administered. Conventional techniques for monitoring blood glucose levels, however, leave much to be desired. One conventional technique, for example, requires that the patient draw blood, typically by pricking the finger. The drawn blood is then analyzed by a portable device to determine the blood glucose level. The technique can be painful and therefore can significantly discourage the patient from periodically checking blood glucose levels. Moreover, since an external device is required to analyze the blood, there is the risk that the patient will neglect to keep the device handy, preventing periodic blood glucose level monitoring. For insulin-dependent diabetics, failure to properly monitor blood glucose levels can result in improper dosages of insulin causing, in extreme cases, severe adverse health consequences such as a ketoacidotic diabetic coma, which can be fatal. Accordingly, there is a significant need to provide a reliable blood glucose monitoring technique, which does not rely on the patient to monitoring his or her own glucose levels and which does not require an external analysis device.
In view of the many disadvantages of conventional external blood glucose monitoring techniques, implantable blood glucose monitors have been developed, which included sensors for mounting directly within the blood stream. However, such monitors have not achieved much success as the glucose sensors tend to clog over very quickly. Thus, an implantable device that would continually and reliably measure blood glucose levels without requiring glucose sensors would be very desirable. Moreover, as with any implantable device, there are attended risks associated with implanting the blood glucose monitor, such as adverse reactions to anesthetics employed during the implantation procedure or the onset of subsequent infections. Hence, it would be desirable to provide for automatic blood glucose level monitoring using medical devices that would otherwise need to be implanted anyway, to thereby minimize the risks associated with the implantation of additional devices. In particular, for patients already requiring implantation of a cardiac stimulation device, such as a pacemaker or ICD, it would be desirable to exploit features of electrical cardiac signals routinely detected by the implantable device for use as a proxy to estimate blood glucose levels.
Two potential proxies for the electrocardiographic monitoring for blood glucose levels have been investigated but are not attractive by themselves. One potential proxy for blood glucose levels is the corrected QT interval (QTc); another is T-wave amplitude. Both vary to a certain extent as a function of the blood glucose levels. More specifically, QTc interval tends to decrease with increasing blood glucose levels, at least up to a certain blood glucose level (beyond which the QTc interval does not change.) T-wave amplitudes tend to increase with increasing blood glucose levels, at least for relatively low blood glucose levels. At higher glucose levels, however, T-wave amplitude tends to decrease with increasing blood glucose level. Hence, QTc interval appears to be effective as a proxy for blood glucose levels only at low levels. Meanwhile, T-wave amplitude behavior is bimodal as it can be lowered by low glucose levels as well as by high glucose levels and hence appears to be ambiguous and ineffective as a proxy.
Thus, heretofore, QTc interval and T-wave amplitude have not been effectively exploited in the monitoring of blood glucose levels. However, as QTc interval and T-wave amplitude each appear to be the affected by blood glucose levels, it would be desirable to provide an improved technique which, despite the individual deficiencies of QTc intervals and T-wave amplitudes, nevertheless achieves reliable detection of the blood glucose levels, and it is this end that aspects of the invention are drawn. In particular, aspects of the invention are directed to providing an implantable cardiac stimulation device with the capability of monitoring blood glucose levels based upon electrocardiographic signals. Other aspects of invention are directed to providing a system and method for programming and calibrating the implanted device for use with individual patients to ensure reliable and accurate operation of the device.
Insofar as exploiting features of electrocardiographic signals for the purposes of blood glucose level monitoring, at least one patent (U.S. Pat. No. 5,741,211 to Renirie) has alluded to the use of electrocardiographic signal features as a basis for detecting blood glucose levels, particularly QRS and T-waves. Renirie is primarily directed to a Holter-type external monitor, but has some discussion of implantable devices as well. Renirie mentions the possibility of using other features besides QRS and T-waves such as QT intervals and RR intervals but does not specifically indicate the desirability of combining QT intervals and T-waves. Moreover, the techniques of Renirie do not appear to be enabling as to the use of T-waves insofar as implantable device monitoring is concerned. For example, Renirie describes the use of a standard pacemaker lead for the purposes of measuring T-wave amplitudes. However, the conventional pacemaker lead simply does not appear capable of detecting T-wave amplitudes with the requisite degree of accuracy. In addition, Renirie fails to even mention the bimodal response of the T-wave amplitude referred to above or to provide any technique for addressing the ambiguities resulting from using T-wave amplitudes as a proxy for blood glucose levels. Moreover, insofar as QT intervals are concerned, Renirie makes no mention of employing corrected QT intervals. Accordingly, despite the speculative teachings of Renirie, significant technical challenges remain in implementing a working system that can optimally and reliably detect blood glucose levels based upon T-waves and QT intervals. Accordingly, still other aspects of the invention are directed toward overcoming the many technical challenges needed to provide a working system for detecting blood glucose levels via T-waves and QT intervals within an implantable medical device.